Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
  • C07F1/00—Compounds containing elements of Groups 1 or 11 of the Periodic Table
  • C07F1/005—Compounds containing elements of Groups 1 or 11 of the Periodic Table without C-Metal linkages

Definitions

• This invention relates to a novel chiral copper complex and to a process for the production of an optically active alkyl cyclopropanecarboxylate using the novel chiral copper complex as a catalyst.
• this invention relates to a novel chiral copper complex which is produced by the reaction of a chiral copper complex of the formula (1): ##STR2## wherein R 1 is (a) alkyl group, or (b) aralkyl group; R 2 is (a) 2-alkoxyphenyl group, or (b) 2-alkoxy-5-alkylphenyl group; either one of X 1 and X 2 is (a) hydrogen atom, (b) halogen atom, (c) alkyl group, (d) alkoxy group, or (e) nitro group, or adjacent X 1 and X 2 together form a benzo group, with a mono-substituted hydrazine of the formula (2):
• R 3 is (a) aryl group, (b) aralkyl group, or (c) alkyl group.
• This invention further relates to a process for the production of an optically active alkyl cyclopropanecarboxylate which comprises the reaction of an alkyl diazoacetate of the formula (3):
• R is an alkyl group, with a prochiral olefin of the formula (4): ##STR3## wherein each one of A, B, P and Q is selected from the group consisting of (a) hydrogen atom, (b) alkyl groups, (c) aralkyl groups, (d) aryl groups, (e) alkenyl groups, (f) alkyl groups containing halogen atom(s), and (g) alkenyl groups containing halogen atom(s), in the presence of a catalytic amount of the novel chiral copper complex as is produced as above.
• optically active cyclopropanecarboxylic acids are important intermediates in the production of pharmaceuticals and agrochemicals.
• (+)-2,2-dimethyl-3-(2-methyl-1-propenyl)cyclopropanecarboxylic acid i.e.
• chrysanthemic acid is an acid component of naturally occurring insecticide, chrysanthemum flower extract, and is industrially produced as an intermediate of synthetic pyrethroid; (+)-2,2-dimethyl-3-(2,2-dichlorovinyl or 2,2-dibromovinyl)-cyclopropanecarboxylic acid is known to be more effective than (+)-chrysanthemic acid as an acid component of the said insecticides; (+)-2,2-dimethyl-3-(2,2,2-trichloroethyl or 2,2,2-tribromethyl)-cyclopropanecarboxylic acid can be a precursor for the above-mentioned compound; and (+)-2,2-dimethylcyclopropane-carboxylic acid has been discovered as an effective constituent of a dehydropeptitase inhibitor for a new type of antibiotics such as Thienamycin derivatives (Japanese Patent Kokai Nos. 40669/80 and 51023/80).
• the methods are available for the production of an optically active cyclopropanecarboxylic acids.
• One is an optical resolution of racemic mixture and the other is a direct asymmetric synthesis.
• the latter can be more efficient than the former.
• asymmetric synthesis using chiral metal complexes is as important as asymmetric reaction utilizing enzymes.
• prochiral olefins of the general formula (4) give optically active alkyl cyclopropanecarboxylates of the general formulas (5) and (6).
• A, B, P and Q are as defined as before.
• alkyl diazoacetates are explosive compounds. It is necessary, therefore, to keep the concentration of this compound in the reaction system as low as possible.
• alkyl diazoacetate is usually added dropwise to a mixture of olefin and catalyst. The decomposition of the diazoacetate can be monitored by the nitrogen gas evolved. Further, it is necessary that the copper complex used as a catalyst should be activated beforehand so that it reacts smoothly with alkyl diazoacetate.
• the following method has been employed: A mixture of the copper complex, olefin and a small amount of alkyl diazoacetate is gradually heated to 70°-80° C. until the evolution of nitrogen gas is observed.
• the copper complex once activated is sensitive enough to decompose alkyl diazoacetate instantly even at a lower temperature.
• the heating operation itself can not be applicable. This is the reason why a more secure and a more safe method than the heat-activation is required.
• the new complex of the general formula (7) is supposed to be a copper (I) complex.
• the four coordination sites of the copper (I) is occupied by a Schiff base as a tridentate ligand and by a half of diazene R 3 NH ⁇ NH as a bidentate ligand.
• the reaction of hydrazine with a divalent inorganic copper salt produces a diazene-copper (I) complex [J. Am. Chem. Soc., 92, 428 (1970) and Accounts Chem. Res. 4, 193 (1971)].
• the main feature of this invention is the discovery of a novel chiral copper complex produced by reacting a chiral copper complex of the general formula (1) with a monosubstituted hydrazine of the general formula (2), and its application, as a catalyst, to the asymmetric synthesis of an alkyl cyclopropanecarboxylate.
• the alkyl groups means those containing 1 to 8 carbon atoms, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, 2-butyl, t-butyl, hexyl, octyl, etc., however, lower alkyl groups containing 1 to 4 carbon atoms are suitable.
• the aralkyl groups are phenylalkyl groups, in other words, alkyl groups of 1 to 3 carbon atoms substituted by a phenyl group, for example, benzyl group.
• the aryl groups are phenyl, tolyl, xylyl and so on.
• the alkoxy groups are those containing 1 to 8 carbon atoms such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, t-butoxy, hexyloxy, octyloxy, etc.
• the halogen atoms are chlorine atom and bromine atom.
• preferable 2-alkoxyphenyl groups are 2-methoxyphenyl; 2-ethoxyphenyl; 2-propoxyphenyl; 2-isopropoxyphenyl; 2-butoxyphenyl; 2-t-butoxyphenyl and 2-octyloxyphenyl; and preferable examples of 2-alkoxy-5-alkyl-phenyl groups include 2-methoxy-5-methylphenyl; 2-butoxy-5-methylphenyl; 5-methyl-2-octyloxyphenyl; 2-butoxy-5-t-butylphenyl; and 5-t-butyl-2-octyloxyphenyl.
• the chiral copper complex of the general formula (1) can be produced by the reaction of a chiral Schiff base of the general formula (8): ##STR7## wherein R 1 , R 2 , X 1 and X 2 are as defined before, with a suitable cupric salt (U.S. Pat. No. 4,029,683).
• Examples of the chiral Schiff base of the general formula (8) include the following compounds. Either (R) from or (S) form may be used: N-salicylidene-2-amino-1,1-di(2-methoxyphenyl)-3-phenyl-1-propanol; N-salicylidene-2-amino-1,1-di(2-isopropoxyphenyl)-3-phenyl-1-propanol; N-salicylidene-2-amino-1,1-di(2-butoxy-5-t-butylphenyl)-3-phenyl-1-propanol; N-salicylidene-2-amino-1,1-di(2-butoxy-butoxy-5-t-butylphenyl)-1-propanol; N-salicylidene-2-amino-1,1-di(2-butoxy-butoxy-5-t-butylphenyl)-1-propanol; N-salicy
• the chiral Schiff base (8) is produced by the reaction of a chiral amino alcohol of the general formula (9) with a salicylaldehyde derivative of the general formula (10). ##STR8## wherein R 1 , R 2 , X 1 and X 2 are as defined before.
• salicylaldehyde derivatives (10) the following compounds can be cited as examples: salicylaldehyde; o-vanillin; 3-ethoxy-salicylaldehyde; 3,5-dibromosalicylaldehyde; 5-chlorosalicylaldehyde; 3-nitrosalicylaldehyde; 3-isopropyl-6-methylsalicylaldehyde; 2-hydroxy-1-naphthaldehyde; 1-hydroxy-2naphthaldehyde; etc.
• the novel chiral copper complex of this invention is produced by the reaction of a chiral copper complex of the general formula (1) with a monosubstituted hydrazine of the general formula (2).
• This reaction is usually carried out in a solvent and is completed within 30 minutes.
• the required amount of the monosubstituted hydrazine (2) is 0.5 mol per one gram atom of the copper.
• Suitable solvents include aromatic hydrocarbons such as benzene, toluene, xylene, etc.; aliphatic hydrocarbons such as pentane, hexane, heptane, etc.; halogenated hydrocarbons such as methylene chloride, ethylene chloride, chlorobenzene, etc. or a mixture of the above solvents.
• Prochiral olefins (4) may be used also as solvents.
• the reaction system should be free from any kind of oxidant such as oxygen.
• the alkyl diazoacetate to be used as a starting material in this reaction is of the formula (3):
• R is an alkyl group, preferably ethyl or t-butyl.
• the alkenyl groups are those containing 2 to 6 carbon atoms such as vinyl or isobutenyl group.
• alkyl groups or alkenyl groups containing halogen atom(s) are chloromethyl, 2,2,2-trichloroethyl, 2,2,2-tribromoethyl, 2,2-dichlorovinyl, etc.
• prochiral olefins of the general formula (4) include 1-substituted ethylene derivatives such as 1-octene; styrene; 4-chloro-1-butene, etc.; 1,1-disubstituted ethylene derivatives such as isobutylene; 1,1-diphenylethylene; ⁇ -methylstyrene, etc.; trans-1,2-disubstituted ethylene derivatives such as t-4-octene; t- ⁇ -methylstyrene; t-silibene, etc.; cis-1,2-disubstituted ethylene derivatives such as c-2-pentene; c-2-heptene; c- ⁇ -methylstyrene, etc.; 1,1,2-trisubstituted ethylene derivatives such as 2-methyl-2-butene; 2-methyl-1-phenyl-1-propene; 2,5-dimethyl-2,4-hexadiene; 1,1-d
• the novel chiral copper complex produced by the reaction of a chiral copper complex of the general formula (1) with a monosubstituted hydrazine of the general formula (2) by the above-mentioned method is used as the catalyst. At this time, there is no need of isolating the novel chiral copper complex prior to the reaction.
• a prochiral olefin of the general formula (4) is dissolved in a catalyst solution prepared beforehand using a solvent, and then a diazoacetic acid ester is added dropwise.
• a diazoacetic acid ester is added dropwise to a solution obtained by reacting a chiral copper complex of the general formula (1) with a monosubstituted hydrazine of the general formula (2) in a mixture of said olefin and a solvent or in said olefin only.
• the suitable amount of the chiral copper complex of the general formula (1) is in the range of 0.01 to 0.0001 equivalent based on the diazoacetic acid ester.
• the feasible reaction temperature is between 0° C. and the boiling point of the solvent used, and the suitable temperature is usually between 0° C. and 50° C.
• optically active cyclopropanecarboxylic acid esters of the general formulas (5) and (6) can be isolated by a usual method, for example, by distillation.
• alkyl cyclopropanecarboxylate of the general formulas (5) and (6) no special explanation is needed because they are cyclo-adducts of alkoxycarbonylcarbene to the olefin of the general formula (4).
• 2,2-dimethylcyclopropanecarboxylic acid ester isobutylene; chrysanthemic acid ester (2,5-dimethyl-2,4-hexadiene); 2,2-dimethyl-3-(2,2-dichlorovinyl)cyclopropanecarboxylic acid ester (1,1-dichloro-4-methyl-1,3-pentadiene); and 2,2-dimethyl-3-(2,2,2-trichloroethyl)cyclopropanecarboxylic acid ester (1,1,1-trichloro-4-methyl-3-pentene).
• Example 2 Exactly the same operation as in Example 1 was conducted, using t-butylhydrazine (8 mg, 0.5 molar equivalent to one g atom of copper) in place of phenylhydrazine (10 mg).
• the optical rotation ⁇ 546 of thus produced pale yellow solution was -0.011° (1 cm).
• ethyl diazoacetate (0.12 g) was added to this solution, quantitative amount of nitrogen gas (24 ml) was evolved instantaneously.
• a toluene solution (40.0 g) of ethyl diazoacetate (16.15 g, 141.7 mmol) purified by distillation was added dropwise under stirring at 40° C., in the course of 7 hours. During these hours, isobutylene gas (33 g) was blown into the solution. The evolution of nitrogen gas started as soon as the addition was started, and at the end of addition, a quantitative amount of nitrogen gas (3.4 liters) was evolved. The reaction mixture was heated to 80° C. to evaporate an excess of isobutylene.
• the resulting mixture (105.2 g) was analyzed by gas chromatography to reveal that the content of ethyl 2,2-dimethylcyclopropanecarboxylate was 15.7% or 16.5 g, and the yield based on ethyl diazoacetate was calculated to be 82.0%.
• the ester was isolated by distillation under reduced pressure (boiling point 80° C./60 mmHg) to show a specific optical rotation [ ⁇ ] D of +105.6° (c 2.0, chloroform). Based on the specific optical rotation [ ⁇ ] D +120° of the optically pure sample, the optical purity of the product was calculated to be 88.0%.
• the amount of ethyl chrysanthemate produced was 9.95 g by gas chromatography and the yield based on ethyl diazoacetate was 67.7%.
• the e.e. was calculated to be 66.1% for the cis isomer and 72.8% for the trans isomer.
• the amount of ethyl 2,2,3-trimethylcyclopropanecarboxylate produced was estimated to be 22.9 g by gas chromatographic analysis, and the yield based on ethyl diazoacetate was calculated to be 70.0%.
• a sample isolated by distillation (boiling point): 105° C./100 mmHg) showed a cis/trans ratio of 79/21 and an optical rotation [ ⁇ ] D of -44.7° (neat, 1 dm).
• the ester was hydrolyzed with a 0.9 equivalent of alkali.
• the unreacted ester recovered (6%) was shown to be cis-isomer having an optical rotation [ ⁇ ] D of -53.0° (neat, 1 dm).
• the carboxylic acid (92%) obtained from aqueous portion showed a a specific optical rotation [ ⁇ ] D of -68.6° (c 1.8, chloroform).
• Cis-2,2,3-trimethylcyclopropanecarboxylic acid obtained by alkaline hydrolysis of the above cis-ester showed a specific optical rotation [ ⁇ ] D of -69.31° (c 2.3, chloroform).
• optically active 2,2,3-trimethylcyclopropanecarboxylic acids reference may be made to Agr. Biol. Chem., 37, 2235 (1973).
• the amount of t-butyl chrysanthemate produced was estimated to be 6.45 g gas chromatography, and the yield based on t-butyl diazoacetate was 72%.
• the amount of ethyl 2,2-dimethyl-3-(2,2,2-trichlor-ethyl)-cyclopropanecarboxylate produced was estimated to be 2.73 g by gas chromatography and the yield based on ethyl diazoacetate was 50%.
• Ethyl 2,2-dimethyl-3-(2,2,2-trichloroethyl)-cyclopropanecarboxylate was hydrolyzed with caustic potash to give 2,2-dimethyl-3-(2,2-dichlorovinyl)-cyclopropane-carboxylic acid, and was converted into the diastereomeric (+)-octyl ester, which was analyzed by gas chromatography. The results were: (+)-cis, 83.6%; (-)-cis, 3.9%; (+)-trans, 7.5% (-)-trans, 5.0%. The e.e. was calculated to be 91% for the cis isomer and 20% for the trans isomer.
• the amount of the ethyl 2-phenylcyclopropanecarboxylate produced was estimated to be 6.26 g by gas chromatography, and the yield based on ethyl diazoacetate was 75%.
• the amount of ethyl 2-hexylcyclopropanecarboxylate produced was estimated to be 5.05 g by gas chromatography, and the yield based on ethyl diazoacetate was 58%.

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• 1983
  • 1983-06-03 JP JP58099955A patent/JPS59225194A/ja active Granted
• 1984
  • 1984-05-24 US US06/614,224 patent/US4552972A/en not_active Expired - Lifetime
  • 1984-05-31 EP EP84303662A patent/EP0128012B1/en not_active Expired
  • 1984-05-31 DE DE8484303662T patent/DE3461374D1/de not_active Expired
• 1985
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